Chapter 1: Introduction to Antibiotic Use

Antibiotic Resistance is a growing global public health threat that is imposing serious effects on management of the infectious diseases. The World Health Organization (WHO) and other international bodies identified antibiotic resistance as the biggest emerging threat for the globe, another pandemic. A National Strategy for Antimicrobial Resistance Containment (ARC) in Bangladesh was developed and approved by the National Steering Committee (NSC) and the National Technical Committee (NTC) with further recommendation of developing a National Action Plan (NAP). The causative microbes of common infectious diseases of Bangladesh are resistant to antibiotics, which include acute respiratory infection (ARI), gastrointestinal infection, tuberculosis (TB), urinary tract infections (UTI), neonatal infections (sepsis), ear infections (otitis media), typhoid fever, and skin & soft tissue infections (SSTIs). Due to lack of standard culture facility, diagnosis and treatment of common infections are mostly empirical. Consequently, the information that we need to design evidence-based intervention to contain antibiotic resistance is currently unavailable in Bangladesh. On this backdrop, Bangladesh has planned to develop a national standard treatment guideline for use of antibiotic.

1.1.1.    Goal: 

To prevent inappropriate use of antibiotic.

1.1.2.    The Objectives:

1.1.2.1.      To recommend treatment for common clinical infections requiring antibiotic therapy 

1.1.2.2.      To promote “AWaRe” classification and approach at all level before prescribing an antibiotic

1.1.2.3.      To promote rational use of antibiotics

1.1.2.4.      To serve as a tool of antimicrobial stewardship in the hospitals

Methodology:

Introduction:

Bangladesh has developed a national strategy for Antimicrobial Resistance Containment (ARC). Based on the strategy, a national action plan has been formulated that has emphasized an integrated approach during implementation, ie; one health approach. The overall aim of the STG was to create a clinical practice guideline with recommendations for common infectious diseases to improve antimicrobial prescribing empirically using an evidence based approach. On this backdrop, initiative has been taken to formulate a guideline on antimicrobial use, the pertinent scientific literature on those topics as systemically searched and summarized.

Group member selection and meeting process:

CDC is leading the initiative and an introductory meeting was arranged. A work group was appointed and assembled to be responsible for the development of the guideline. The work group consisted of domain experts, including individuals with expertise in infectious disease, internal medicine, critical care medicine, paediatrics, surgery, otolaryngology, ophthalmology, orthopaedics, obstetrics & gynaecology, microbiology, pharmacology and epidemiology. The working group members of this guideline are listed at the beginning of this report. USAID, MTaPs was closely collaborated with CDC throughout the process. Biweekly meeting of the core working group was held both virtually and physically for the topic discussion, guideline development process and consensus development.

Evidence selection, appraisal and presentation:

We first defined the topics, goals and objectives for the guideline and the core working group performed literature searches, articles screening and summarized the evidence. After reviewing all the articles, evidence profiles and data from related resources, a list of commonly occurring infectious diseases of Bangladesh was selected and a template to collect data was prepared and the template was disseminated to the potential sources. The disease pattern of the country was reviewed to identify the important infectious diseases based on their burden. Microbial sensitivity pattern was collected from available authentic sources. A template of summary tables was categorized by the preferred and alternative antibiotics for empirical treatment incorporating the AWaRe classification of antibiotics with the likely causative agents. In the case of combination treatment, the AWaRe classification was labelled beside the antibiotics. A consultative workshop on STG development was held on 5th October 2020 and the proposed template was shared with the key stakeholders. An evidence-based guideline incorporating available sensitivity data of Bangladesh and using pre-existing guidelines, a proposed STG was drafted including empiric judgment along with the feedback from the core working group. The last version was developed on 6th January 2021 and the draft was sent to the professional associations for their opinions. Then workshop on the finalization of this guideline was arranged on 19th September 2021 and collected expert feedback through “Delphi technique”. CDC staff then independently reviewed the tables of evidence prepared by the subject matter experts, individual comments from the participants and professional organizations, and existing guidelines from other organizations.

Recommended preferred regimens should be used empirically and alternative regimens can be considered in instances of notable drug allergy or other medical contraindications to the preferred regimens. The treatment can be adjusted according to the culture sensitivity report where the laboratory facilities are available.

Scope of this guideline:

This guideline is going to be used for empirical antimicrobial treatment before getting culture sensitivity result or in hospitals where regular microbiology testing is not available.

The hospitals where microbiology testing is available should develop their own protocol for empirical antibiotic therapy using their institutional antibiogram.

For infectious diseases where separate national guidelines are available, those guidelines should be preferred over this guideline.

Infections remain a common cause of presentation to the outpatient department (OPD) and inpatient (IPD) admissions to the hospital. Antibiotics are widely being prescribed to treat infections, both in the community and hospital setting. Selection of an appropriate antibiotic can be challenging to the clinician. Consequently, understanding the basic principles of antibiotic therapy is important to ensure optimal outcome and to reduce selective pressure on antibiotics, which may be associated with the development of antibiotic resistance. The available evidence suggests that, when antibiotic use is warranted, choosing the therapy most likely to achieve clinical cure and treating for the shortest length of time to achieve clinical and microbiological efficacy. It will result in a lower incidence of retreatment and lower incidence of antibiotic resistance. The rational use of medicines has been defined by the WHO as requiring that patients receive medications appropriate to their clinical needs, in doses that meet their own requirements, for an adequate time, and at the lowest cost to them and their community.

A thorough clinical assessment of the patient is imperative to ascertain the underlying reason. Where appropriate and clinically indicated, the initial assessment should be supported by relevant laboratory investigations (blood, urine, sputum, wound swab) to establish a definitive microbiological diagnosis and to determine the susceptibility of the organism to various antibiotics. The routine use of antibiotics to treat fever (less than 5 days) is inappropriate, as not all fever is caused by infection and antibiotics are only indicated for bacterial infections. Antibiotics should not be prescribed when bacterial infections are unlikely, such as for common cold, coughs and bronchiolitis and others.

1.2.1.         Steps of Rational Antibiotic Use

1.2.1.1.      Step 1: Clinical Diagnosis

Making a clinical diagnosis is often not given enough importance leading us to advice series of laboratory investigations. A clinical diagnosis most often helps us to predict causative pathogens fitting in to a clinical syndrome which would tailor the correct antibiotic rather than blindly relying on fever, procalcitonin levels, WBC counts, cultures or radiology to make a diagnosis of infection. Our thought process here should be:

• Diagnosis of infection
• Is it an infection?
• A risk assessment of how likely is it that the patient has an infection?
• What are the possible non-infectious mimics?
• Have we taken the appropriate cultures to confirm the final diagnosis?

1.2.1.2.      Step 2: Limiting empiric antibiotic therapy

Limiting empiric antibiotic therapy to moderate or severely ill patients. Generally, empiric antibiotic therapy is recommended for a selected group of patients as described below after taking appropriate cultures.

• Febrile neutropenia
• Severe sepsis and septic shock
• Community acquired pneumonia
• Ventilator associated pneumonia
• Aspiration and suppurative pneumonia
• Enteric fever
• Bacterial meningitis

Hence, it is important to start smart and then focus, i.e., evaluate if empiric therapy can be justified or de-escalated and then make a plan with regard to the duration of therapy.

1.2.1.3.      Step 3: Know your microbes 

Approach includes

• Identify the clinical syndrome
• Elucidate possible sources of infection
• Predict possible microbial pathogens
• Predict the local resistance pattern based on institutional antibiogram (if available)

1.2.1.4.      Step 4: Choose the appropriate antibiotic

Approach includes

• Based on possible resistant patterns and the spectrum of the antibiotic
• Use the correct dose, route and duration
• Ensure chosen antibiotic has adequate tissue penetration at the site of infection
• Optimize pharmacokinetics/pharmacodynamics parameters according to comorbidities

1.2.1.5.      Step 5: De-escalation/modification

• Modify empiric broad spectrum antibiotics depending on culture and antibiotic susceptibility result and patient status. Approach includes:
  • the empiric antibiotic(s) that were started are stopped
  • or reduced in number (e.g. combination therapy to a single agent)
  • and/or narrowed in spectrum (broad spectrum to narrow spectrum)
  • switching to new agent based on susceptibility result
• Stop polymyxins and glycopeptides if no carbapenem resistant organisms (CRO) or methicillin resistant Staphylococcus aureus (MRSA) identified on cultures
• Avoid double or redundant Gram-negative or Gram-positive or anaerobic coverage
• Discontinue antibiotics if a non-infectious mimic identified
• Change IV to oral antibiotics
• De-escalation is safe in all patients including febrile neutropenia and septic shock and reduces mortality and length of hospital stay.

1.2.1.6.      Step 6: No antibiotics in the following clinical situations

• Respiratory tract syndromes:
  • Viral pharyngitis
  • Viral rhinosinusitis
  • Viral bronchitis/bronchiolitis
  • Non-infectious cardio-pulmonary syndromes misdiagnosed as pneumonia
• Skin and Soft Tissue Infections:
  • Subcutaneous abscesses
  • Lower extremity stasis dermatitis
• Asymptomatic bacteriuria and pyuria including in catheterized patients
• Microbial colonization and culture contamination (Check culture report for colony count and others)

The 2019 WHO AWaRe Classification Database was developed on 1st October 2019 according to the recommendation of the WHO Expert Committee on Selection and Use of Essential Medicines. It includes details of 180 antibiotics classified as Access (A), Watch (Wa) or Reserve (Re), their pharmacological classes, Anatomical Therapeutic Chemical (ATC) codes and WHO Essential Medicines List status. It is intended to be used as a uniform and interactive tool for countries to better support antibiotic monitoring and optimal use.

Improving use of antibiotics through antibiotic stewardship is one of the key interventions necessary to curb the further emergence and spread of antimicrobial resistance (AMR). It is also important for ensuring appropriate treatment.

For that reason, WHO in 2017 introduced the Access, Watch, Reserve (“AWaRe”) classification of antibiotics in its Essential Medicines List. The classification is a tool for antibiotic stewardship at local, national and global levels with the aim of reducing antimicrobial resistance.

1.3.1. ACCESS GROUP ANTIBIOTICS

This group includes antibiotics that have activity against a wide range of commonly encountered susceptible pathogens while also showing lower resistance potential than antibiotics in the other groups. There 48 antibiotics in this group according to WHO. These antibiotics are preferable than other groups of antibiotics. 

1.3.2. WATCH GROUP ANTIBIOTICS

This group includes antibiotics that have higher resistance potential and includes most of the highest priority agents among the critically important antimicrobials for human medicine and/or antibiotics that are at relatively high risk of selection of bacterial resistance. Antibiotics in Watch group should be used cautiously when access group of antibiotics are not appropriate for that infection.

1.3.3. RESERVE GROUP ANTIBIOTICS

This group includes antibiotics and antibiotic classes that should be reserved for treatment of confirmed or suspected infections due to multi-drug-resistant organisms. Antibiotics in Reserve group should be treated as “last resort” options, which should be accessible, but their use should be tailored to highly specific patients and settings, when all alternatives have failed or are not suitable. These medicines could be protected and prioritized as key targets of national and international stewardship programs involving monitoring and utilization reporting, to preserve their effectiveness.  

1.3.4. Measuring antibiotic consumption  

By quantifying the use of antibiotics in each of the AWaRe categories (relative or absolute) allows some inference about the overall quality of antibiotic use in a given country. Countries should first compare national / regional antibiotic use using absolute consumption data, and then relative use according to AWaRe categories. The combination of both absolute and relative consumption by category allows simple benchmarking (e.g. an overuse of Watch antibiotics can become immediately apparent and a reduction in Watch antibiotics can be identified as a target for antibiotic stewardship interventions) and assessment of trends over time (to evaluate the impact of interventions).

1.3.5. Improving use of antibiotics for universal health coverage

Access to quality, safe and affordable medicines and health products is a key contribution to Universal Health Coverage (UHC) and the triple billion target set by WHO’s 13th General Program of Work (GPW). Within the 13th GPW is an indicator, based on AWaRe, which specifies a country-level target of at least 60% of antibiotic consumption being from medicines in the Access Group. This indicator was included to monitor access to essential medicines and progress towards UHC.